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ヒト癌におけるP16-COK-Rb細胞回転異常に関する病理学的研究

人类癌症P16-COK-Rb细胞旋转异常的病理研究

基本信息

批准号：
11470049
负责人：
NAKAJIMA Takashi
金额：
$ 2.75万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470049/
关键词：
Human cancers Cell cycle regulator proteins RB pathway p53 pathway Immunohistochemistry Rb経路細胞回転 p16蛋白 CDK pRb蛋白 p53蛋白

项目摘要

Expression of cell cycle regulatory proteins in both the RB and p53 pathways were investigated in lung, esophageal and oral cancers using immunohisto-chemical techniques. In squamous cell carcinoma (SCC) of lung, abnormality of p16 expression was prominent at the frequency of 78% in the RB pathway. On the other hand, strong and diffuse p53 immunoreactivity was seen in 60% of SCCs, which seemed to have point mutation of the p53 gene. In comparing clinicopathological status with the immunohistochemical results, strong p53 expression was frequently observed in higher stages of SCC, with the developing tumor located in the central field of the lung. Similarly, the frequency of p14ARF expression was high in centrally developed SCC.In stage I adenocarcinoma of the lung, abnormality of the RB pathway was not frequent. However, abnormal expression of p14ARF and MDM2 was characteristic features in the p53 pathway. Overexpression of MDM2 protein was characteristic feature in stage I adenocarcinomas, especially in well differentiated ones. These findings elucidate that cell cycle abnormality is mostly depend on p53 pathway other than RB pathway in stage I adenocarcinomas of lung.The abnormality of both RB and p53 pathways was also observed in esophageal and oral squamous cell carcinomas. Therefore, abnormality in RB and p53 pathways was essential for development of human cancers.

利用荧光化学技术研究了RB和p53通路中细胞周期调节蛋白在肺癌、食管癌和口腔癌中的表达。在肺鳞癌中，RB通路中p16表达异常的频率为78%。另一方面，在60%的SCC中观察到强的和弥漫性的p53免疫反应，其似乎具有p53基因的点突变。在比较临床病理状态与免疫组化结果，强p53表达经常观察到在较高阶段的SCC，与发展中的肿瘤位于中央领域的肺。同样，p14 ARF在中央型SCC中表达频率较高，而在I期肺腺癌中RB通路的异常并不常见。而p14ARF和MDM2的异常表达是p53通路的特征性特征。MDM2蛋白的过度表达是I期腺癌的特征性特征，尤其是在高分化腺癌中。这些结果表明，在I期肺腺癌中，细胞周期异常主要依赖于p53通路而非RB通路，在食管癌和口腔鳞癌中，RB和p53通路均异常。因此，RB和p53通路的异常对于人类癌症的发展是必要的。